R&D Day 2020

R&D Day 2020

DAIICHI SANKYO CO., LTD.

Sunao ManabePresident and CEO

December 15th, 2020

Forward-Looking Statements

2

Management strategies and plans, financial forecasts, future projections and policies, and R&D information that Daiichi Sankyo discloses in this material are all classified as Daiichi Sankyo’s future prospects. These forward looking statements were determined by Daiichi Sankyo based on information obtained as of today with certain assumptions, premises and future forecasts, and thus, there are various inherent risks as well as uncertainties involved. As such, please note that actual results of Daiichi Sankyo may diverge materially from Daiichi Sankyo’s outlook or the content of this material. Furthermore, there is no assurance that any forward-looking statements in this material will be realized. Regardless of the actual results or facts, Daiichi Sankyo is not obliged and does not have in its policy the duty to update the content of this material from the date of this material onward.

Some of the compounds under discussion are investigational agents and are not approved by the FDA or any other regulatory agency worldwide as a treatment for indications under investigation. Efficacy and safety have not been established in areas under investigation. There are no guarantee that these compounds will become commercially available in indications under investigation.

Daiichi Sankyo takes reasonable care to ensure the accuracy of the content of this material, but shall not be obliged to guarantee the absolute accuracy, appropriateness, completeness and feasibility, etc. of the information described in this material. Furthermore, any information regarding companies, organizations or any other matters outside the Daiichi Sankyo Group that is described within this material has been compiled or cited using publicly available information or other information, and Daiichi Sankyo has not performed in-house inspection of the accuracy, appropriateness, completeness and feasibility, etc. of such information, and does not guarantee the accuracy thereof.

The information described in this material may be changed hereafter without notice. Accordingly, this material or the information described herein should be used at your own judgment, together with any other information you may otherwise obtain.

This material does not constitute a solicitation of application to acquire or an offer to sell any security in the United States, Japan or elsewhere.

This material disclosed here is for reference purposes only. Final investment decisions should be made at your own discretion.

Daiichi Sankyo assumes no responsibility for any damages resulting from the use of this material or its content, including without limitation damages related to the use of erroneous information.

A Year from R&D Day 2019: 3 ADCs are Progressing Steadily

3

DS-8201

Steady progress of 3 ADCs gains confidence for achieving our 2025 Vision

Launched in US and JP

DS-1062 U3-1402

Ph1 study is progressing smoothly

Starting pivotal Ph2 studyas well as combination study with osimertinib

Good relationship

Strategic collaboration

Enhancing development plan with AZ Started Ph2 study

Ph1/2 study is progressing smoothly

Additional indication in JPFDA accepted sBLA

Ph2 studies are progressing smoothly

Breast Gastric Lung CRC

A Year from R&D Day 2019: Progress of Alpha Projects

4

DS-7300/DS-6157

Key projects that follow the 3 ADCs are also progressing steadily

Nucleic Acid (ENA®) Immuno-Oncology

Activatedregulatory T cell

DS-1055

GARP

DS's first immuno-oncology project

Different MOA from PD-1 /PD-L1

Ph1 study started in Oct. 2020

DS-5141: TLR anticipated by the end of this year

Non-clinical studies are ongoing for the follow-on DMD projects(exon 44, 50, 51, 53 skipping), andDS-4108 (glycogen storage disease type Ia)

DS-6157 (GPR20-directed ADC)Study ongoing in GIST

Ph1

Ph1

DS-7300 (B7-H3-directed ADC)Study ongoing in 11 different tumor types

B

2' 4'

O

OO

P SOH

O

ENA®

Cash Allocation for Maximizing Shareholder Value

5

Maximize Profitability

as well as Shareholder

Value

SustainableGrowth

Investment for Future

GrowthR&D investment

Capital investment

Maximize future shareholder value through aggressive investment in the pipeline

Enhanced Capital Investment

6

Increasing manufacturing capacity through capital investment and utilizing CMOs, considering commercial manufacturing for the follow-on ADCs

Onahama Plant

Pharmaceutical Company’s Mission: COVID-19 Countermeasures

7

Encouraging data obtained from non-clinical pharmacology studies:Clinical study is planned to start in March 2021

DS original cationic lipidEfficient encapsulation of mRNA in

nanoparticles, and efficient delivery of mRNA to cellsApplicable to pandemic and other

vaccines

DS-5670: LNP-mRNA Vaccine

5-Year Business Plan (FY2021-25): to be Announced Next Spring

8

Maximize the value of 3 ADCs

Strive for sustainable growth

Delivering the science patients deserve

Antoine Yver, MD, MScExecutive VP & Global Head, Oncology R&D

R&D Day December 15, 2020

Agenda

01 Our scientific and competitive environment

02 Our clinical-stage DXd ADCs

03Our transformation towards a biologics and multi-modality Company

10

01

Our scientific and competitive environment

11

How we got here Our path to durable leadership

The decade of targeted therapies. From Herceptin® to Gleevec®,Iressa® and Avastin®… these therapies unleashed the power of suppressing pathways.

The wonders of immune checkpoint inhibition and the power of re-directed T-cell therapy. A glorious decade of IO.

A new era where high-tech pharmacology propels a century-old idea — ADCs.

12

The 2000’s The 2010’s The 2020’s

Degree of integrated, multimodality high-techMOA and high potency payload, hyper-stable linker, exquisite delivery to the tumor, unique bystander potential, world-class protein engineering

Mastery of a new critical pathophysiologyThe receptor dynamic and its pharmacomodulation

“Duration of response” is a direct and the most critical benefit of the DXd design

This can establish true “chemo-free regimen” as mainstay of cancer treatment

13

Uniqueness of the DXd ADC technology platform: durability of effect

The 2020’sADCs from Daiichi Sankyo - what is important?

The competition in ADCs is real…But we’re already tackling what’s next

14

• Gilead (formerly Immunomedics) :sacituzumab govitecan (Trodelvy ®) is a great drug with a bright future

• Merck / Seagen: LIV-1 DAR4 auristatin protease-cleavage ADC

• Pfizer: HER2 DAR4 auristatin (PF-06804103)

• Etc…

We respect our competitors But ADCs are “old news”

We’re ready to blaze the trail: aiming at chemo-free ADC

regimenexploiting the unique biology of

ADCs

Biology of ADCs as key for smart, chemotherapy-free regimen

15

Pharmacological manipulations of ADC/receptor biology

Selecting the right patients and tumors

Predicting outcomes

Designing and enriching treatment protocol and combinations for the right patients

Immediate value of our top 3 ADCsBreast and lung cancers

16

Breast: DS-8201a Lung: DS-1062b Lung: U3-1402c

Swift development of the next 2 ADCs

NSCLC:Post IO/chemo phase 3

NSCLC:IO combination aiming at 1st line

Fast to market development (EGFRm NSCLC)

Combination with osimertinib

As we shape new possibilities for ADCs, we are resolutely focused on our duty: delivering the science patients deserve

Maximization

HER2+ breast cancer, mBC & early breast cancer: a suite of phase 3 trials

HER2 low breast cancer DESTINY-Breast04 read-out FY2021

a DS-8201/trastuzumab deruxtecan (T-DXd); b DS-1062/datopotamab deruxtecan (Dato-DXd); c U3-1402/patritumab deruxtecan (HER3-DXd)

02

17

Our clinical-stage DXd ADCs• DS-8201/trastuzumab deruxtecan (T-DXd)• DS-1062/datopotamab deruxtecan (Dato-DXd)• U3-1402/patritumab deruxtecan (HER3-DXd)• Alpha: DS-7300 (B7-H3), DS-6157 (GPR20), DS-6000 (CDH6), DS-3939 (TA-MUC1)

02

18


DS-8201/trastuzumab deruxtecan (T-DXd)

19

1. GastricJapan approval September 2020 US FDA sBLA under Priority Review with PDUFA of February 28, 2021

2. Breast: The big storyEU CHMP opinion positive opinion (December 11, 2020)Duration of response by monotherapy in end stage is mimicking 1st line mBC triple-therapy

3. Lung cancerHER2 mutant and HER2 expressing

4. IO comboWhy does it matter?

5. ILD safe use

DESTINY-Gastric01An open-label, multicenter, randomized, phase 2 study

20

DESTINY-Gastric01 An open-label, multicenter, randomized phase 2 study (NCT03329690)

GASTRIC

DESTINY-Gastric01: EfficacyJapan approved September 2020, US FDA PDUFA February 28, 2021

21

Source: Shitara et al., Abstract #4513, ASCO 2020; K. Shitara et al, N Engl J Med 2020; 382:2419-2430 (DOI: 10.1056/NEJMoa2004413)

Overall survival

Events/n Median

DS-8201 62/125 12.5 months(95% CI, 9.6-14.3)

Physician’s choice 39/62 8.4 months(95% CI, 6.9-10.7)

HR, 0.59 (95% CI, 0.39-0.88)P = .0097

(prespecified O’Brien-Fleming boundary, P = .0202)

DS-8201 (n = 119) PC (n = 56)

ORR by ICR(CR + PR)

51.3% (n = 61)95% CI, 41.9-60.5; P < .0001

14.3% (n = 8)95% CI, 6.4-26.2

Confirmed ORR by ICR(CR + PR)

42.9% (n = 51)95% CI, 33.8-52.3

12.5% (n = 7)95% CI, 5.2-24.1

GASTRIC

Overall response

DESTINY-Gastric01: SafetyJapan approved September 2020, US FDA PDUFA February 28, 2021

22

TEAEs associated with: DS-8201 (n = 125) PC (n = 62)

Drug discontinuation 15.2% 6.5%

Dose reduction 32.0% 33.9%

Dose interruption 62.4% 37.1%

• 1 drug-related death due to pneumonia with DS-8201 and none with PC

• 12 patients (9.6%) had DS-8201-related ILD/pneumonitis as determined by an independent adjudication committee– Median time to first onset, 84.5 days (range, 36–638 days)– Most were grade 1 or 2 (grade 1, n=3; grade 2, n=6;

grade 3, n=2; grade 4, n=1, no grade 5 events)

Treatment-emergent adverse events

Source: Shitara et al., Abstract #4513, ASCO 2020; K. Shitara et al, N Engl J Med 2020; 382:2419-2430 (DOI: 10.1056/NEJMoa2004413)

GASTRIC

Looking aheadHER2+ advanced gastric cancer plan

Randomized phase 3 study in 2nd line, DS-8201 monotherapy vs. active control

Imminent start

23

DESTINY-Gastric04

DESTINY-Breast01The big story: EU CHMP positive recommendation for ENHERTU

• Submitted in May 2020 and completed, without any ‘no-clock stop’, 7-month start to finish Accelerated assessment schedule

• First breast cancer drug recommended for approval by EMA on the basis of single arm phase 2 data in the past two decades

• Indication : “Enhertu as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens”

24

BREAST

DESTINY-Breast01The big story: duration of response

25

DESTINY-Breast01 An Open-Label, Multicenter, Phase 2 Study (NCT03248492).

BREAST

DESTINY-Breast01The big story: duration of response in late line mBC

26

Intent-to-treat analysis

June 2020 data cutoffDS-8201 5.4 mg/kg(N = 184)

Duration of follow-up, median (range) 20.5 months (0.7-31.4)

Patients remaining on treatment 20.1% (n = 37)

Confirmed ORR by ICR 61.4% (n = 113)(95% CI, 54.0%-68.5%)

Standard of care in first-line mBC:the CLEOPATRA Study in 1st line mBCTHP (trastuzumab, pertuzumab and docetaxel)Duration of response = 20.2 months (95% CI, 16.0 to 24.0)S Swain J Baselga et al NEJM2015

Monotherapy Duration of Response: 20.8 months (median)

Source: S. Modi et al., Abstract #1190; PD3-06, SABCS 2020

BREAST

DESTINY-Breast01: ILD & safety updateILD risk appears to flatten after 12 months

27

n (%)

August 2019 data cutoffDS-8201 5.4 mg/kg (N = 184)

June 2020 data cutoffDS-8201 5.4 mg/kg(N = 184)

Any TEAEDrug-related

183 (99.5)183 (99.5)

183 (99.5)183 (99.5)

TEAE grade ≥3Drug-related

105 (57.1)89 (48.4)

113 (61.4)97 (52.7)

TEAE associated with discontinuation

Drug-related

28 (15.2)

27 (14.7)

34 (18.5)

33 (17.9)

Cumulative Probability of Adjudicated Drug-related Interstitial Lung Disease (ILD)

Source: S. Modi et al., Abstract #1190; PD3-06, SABCS 2020

BREAST

Why does durability matter? An accelerated HER2+ mBC & early breast cancer plan

28

• Clear unmet medical need is to increase overall PFS and further prolong duration of overall response– Brain mets (BM) failure after 1st line THP treatment is

infrequent1: 13.7% (55/402) CNS as first site of progression.

– An aggressive and bold plan aiming at 1st line mBC

1 CLEOPATRA study S Swain J Baselga et al Ann Oncol 2014 Jun;25(6):1116-21.2 EMILIA Study I Krop N Lin et al Ann Oncol 2015:26:113-119.

1st line mBC treatment Potential to be superior to trastuzumab emtansine (T-DM1)

Designing principles & steps for DS-8201 are clear:

• Role of ADC in 2nd line mBC– BM failure after T-DM1 in 2nd line is uncommon2 (2% if

no BM at start of treatment, 22% if BM at start of T-DM1 treatment)2

– The unmet medical need is to improve over T-DM1 outcome: DESTINY-Breast03 in 2nd line mBC

– Event-driven analysis: projected in FY2021 Q2

• Early Breast Cancer: DESTINY-Breast05 post-neoadjuvant trial under way with NSABP et al

BREAST

DESTINY-Breast03 (NCT03529110); DESTINY-Breast05 (NCT04622319)

Why does durability matter? An accelerated HER2 mBC & early breast cancer plan

1st line HER2 mBCTwo routes to improve standard of care

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DESTINY-Breast09: a randomized, active control 1st line phase 3 study DS-8201 monotherapy vs DS-8201 combo vs standard of care [THP]

DESTINY-Breast07 / BEGONIA combination studies stage-gating another combo phase 3 study in 1st line vs THP

BREAST

DESTINY-Breast09 (not yet listed on Clintrials.gov) DESTINY-Breast07 A Phase 1b/2 Study of DS-8201 Combinations in HER2-positive Metastatic Breast Cancer (NCT04538742)

Why does durability matter? An accelerated HER2 mBC & early breast cancer plan

• Global post-neoadjuvant study vs. T-DM1 in collaboration with:– US National Surgical Adjuvant Breast and Bowel Project Foundation (NSABP) – German Breast Group (GBG)– Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-B)– Spain SOLTI Breast Cancer Research Group– Asia, and other global sites

• Residual invasive disease in breast or axillary lymph nodes following neoadjuvant therapy for high risk HER2 early breast cancer

• ~1,600 patients, IDFS (invasive disease-free survival) as primary endpoint

30

DESTINY-Breast05

BREAST

Why does durability matter?Accelerated HER2 low mBC plan

• Late line, post-chemo “entry point”DESTINY-Breast04– Rationale: Phase 1 study confirmed ORR of 37% median duration of response 10.4 months in HER2

low mBC1

– N= 540, vs. Physician Choice (eribulin, gemcitabine, paclitaxel, nab-pac), PFS BICR – Event-driven analysis, projected in FY2021 Q2

• Post endocrine therapy (chemo naïve)DESTINY-Breast06– N=850 vs. Physician Choice (capecitabine, paclitaxel, nab-pac), PFS BICR

• Earlier mBC line– Bold, innovative plan to be announced

Of note: Early breast cancer Adjuvant in HR+ segmentNot our area of focus

311 Modi et al., JCO 2020 Jun 10:38(17): 1887-1896

BREAST

DESTINY-Breast04 (NCT03734029); DESTINY-Breast06 (NCT04494425)

DS-8201: HER2 mutant NSCLCDESTINY-Lung01 study

Efficacy

Patients (N=42)

Confirmed ORR by ICR 61.9% (n=26) (95% Cl, 45.6%-76.4%)

CR 2.4% (n=1)

PR 59.5% (n=25)

SD 28.6% (n=12)

PD 4.8% (n=2)

Not evaluable 4.8% (n=2)

Disease control rate 90.5% (95% Cl, 77.4%-97.3%)

Duration of response, median Not reached (95% Cl, 5.3 months-NE)

PFS, media 14.0 mo (95% Cl, 6.4-14.0 months)

Safety

Treatment-Emergent Adverse Events in >15% of Patients (N=42) • Breakthrough Therapy Designation (BTD) May 2020

• Final analysis of HER2 mutation NSCLC cohort FY2021 H1

32

DESTINY-Lung01 An open-label, multicenter, phase 2 study (NCT03505710)Source: Smit et al., Abstract #9504 ASCO 2020

LUNG

Patients, %

Best Change in Tumor Size

Design to maximize benefit of durabilityAn accelerated HER2 lung cancer plan

HER2 mutant

• DESTINY-Lung01 expansion, with a confirmed US fast-to-market opportunity

• DESTINY-Lung025.4 mg/kg vs 6.4 mg/kg– Based on consultation with

FDA and other health authorities– FSD in FY2020 Q4

• DESTINY-LungXX1st line phase 3 study planning

HER2 expressing

• Next generation IHC under development

• DESTINY-Lung01 IHC expressing cohort enrolled, awaiting maturation

33

LUNG

DESTINY-Lung01 (NCT03505710) DESTINY-Lung02 (NCT04644237)

DS-8201: HER2+ CRC (colorectal cancer)DESTINY-CRC01 study

34

Efficacy

HER2+ Cohort A (N=53)

Confirmed ORR by ICR 45.3% (n=24) (95% Cl, 31.6%-59.6%)

CR 1.9% (n=1)

PR 43.4% (n=23)

SD 37.7% (n=20)

PD 9.4% (n=5)

Not evaluable 7.5% (n=4)a

Disease control rate 83.0% (95% Cl, 70.2%-91.9%)

Duration of response, median Not reached (95% Cl, 4.2 months-NE)

Safety

Treatment-Emergent Adverse Events in >15% of Patients (N=78) • Non-registrational DESTINY-CRC02, testing 5.4 and 6.4 mg/kg

Source: Siena et al., Abstract #4000 ASCO 2020 DESTINY-CRC01 An open-label, multicenter, phase 2 study (NCT03384940)DESTINY-CRC02 (not yet listed on Clintrials.gov)

CRC

Patients, %

Best Change in Tumor Size

DS-8201: Clinical Development PlanBreast cancer

35

Ph 3 ongoing

Ph 2 ongoing

New

Ph 1 ongoing

Completed

Study initiation points for FY2020 H2 are all shown as beginning of H2. Study initiation points for FY2021 are all shown as beginning of FY2021.

As of December 2020 ~FY2019 FY2020 FY2021 Under Discussion

HER2 Positive

Metastatic3L

Metastatic2L

Metastatic1L

Post-neoadjuvant

Neoadjuvant Phase 3

Adjuvant Phase 3

HER2 Low

HR+/HR-

Metastatic Post Chemo

Post-neoadjuvant Phase 3

HR+

MetastaticChemo NaiveMetastaticEndocrine Therapy Phase 3

HR-

Metastatic1L

Neoadjuvant Phase 3

DESTINY-Breast01 monotherapy




DESTINY-Breast07 combination (2L/1L) phase 1

DESTINY-Breast09 combo phase 3

DESTINY-Breast05 monotherapy vs. T-DM1

DESTINY-Breast08 combination phase 1


BEGONIA (durvalumab combination)

DS-8201: Clinical Development PlanGastric and lung cancers

36

Ph 3 ongoing

Ph 2 ongoing

New

Ph 1 ongoing

Completed



Gastric HER2 Positive

Advanced/Metastatic3L~

Advanced/Metastatic2L

Advanced/Metastatic1L Phase 3

Lung

HER2 Expressing


Advanced/Metastatic2L Phase 3 monotherapy

Advanced/Metastatic1L

Phase 3 combination

HER2 Mutated


Advanced/Metastatic1L Phase 3

Expressing/Mutated Early disease Phase 3 combination

DESTINY-Gastric01 monotherapy(HER2 low in exploratory cohort)

DESTINY-Lung01 monotherapy

DESTINY-Lung01 monotherapy

DESTINY-Gastric04 monotherapy phase 3

DESTINY-Lung03 combination phase 1

DESTINY-Lung02 monotherapy phase 2

DESTINY-Gastric02 monotherapy (2L) - West

HUDSON (durvalumab combination)

DESTINY-Gastric03 combination (2L/1L)

DS-8201: Clinical Development PlanCRC and other tumors

37

Ph 3 ongoing

Ph 2 ongoing

New

Ph 1 ongoing

Completed



CRC HER2Expressing

Metastatic3LMetastatic2L Phase 3 combination

Metastatic1L Phase 3 combination

Other Tumors

HER2Expressing

Metastatic2L

Ovarian Phase 2 combination

HER2 Mutated

Metastatic2L

DESTINY-CRC01 monotherapy(HER2 Low in exploratory cohort） DESTINY-CRC02 monotherapy phase 2

DESTINY-PanTumor01 phase 2

DESTINY-PanTumor02

Pembrolizumab combination (breast, NSCLC)

Nivolumab combination (breast, bladder)

DS-8201: Critical short-term phase 3 data forecast

38

DESTINY-Breast02 | HER2 positive mBCvs standard of care

• Event-driven final analysis, projected FY2021 Q2

DESTINY-Breast03 | HER2 positive mBCvs T-DM1

• Event-driven interim analysis, projected FY2021 Q2

DESTINY-Breast04 | HER2 low mBCvs standard of care

• Event-driven final analysis,projected FY2021 Q2

DS-8201: Nivolumab combination in breast cancer2-part, phase 1b, multicenter, open-label study

39

BREAST

DS8201-A-U105 A 2-part, phase 1b, multicenter, open-label study (NCT03523572)

DS-8201 with nivolumab: Efficacy

40

Source: Hamilton et al., Abstract #299; PD3-07 SABCS 2020

Best percent change from baseline in tumor sizeHER2 positive(n=32)

HER2 low(n=16)

Confirmed ORR by ICR [95% Cl]CRPRSDPDNE

59% [41-76] (n=19)3% (n=1)

56% (n=18)31% (n=10)

6% (n=2)3% (n=1)

38% [15-65] (n=6)0

38% (n=6)38% (n=6)13% (n=2)13% (n=2)

DCR, median [95% Cl] 91% [75-98] (n=29) 75% [48-93] (n=12)

DOR, median [95% Cl], months NE [4.1-NE] NE [2.8-NE]

HER2-Positive Cohortn=33

HER2-Low Cohortn=15

DS-8201 with nivolumab: EfficacySpider plots of target lesions, based on ICR

41

Source: Data on file. Preliminary. Daiichi Sankyo unpublished data

HER2 positive breast cancer HER2 low expressing breast cancer

DS-8201 with nivolumab: Safety

42

ILD All TEAEs

10.4 (5)

0

8.3 (4)

0 0

2.1 (1)

0%

5%

10%

15%

20%

25%

Total Grade 1 Grade 2 Grade 3 Grade 4 Grade 5

Patie

nts,

% (#

)

Adjudicated as study-drug related ILD in all Patients Treated at the RDE, N=48a

Source: Hamilton et al., Abstract #299; PD3-07 SABCS 2020 (modified)

0 10 20 30 40 50 60 70 80 90 100

Edema peripheral

Pruritus

Aspartate aminotransferase level increased

Cough

Decreased appetite

Anemia

Vomiting

Diarrhea

Constipation

Alopecia

Fatigue

Nausea

Any TEAE (Nivo related)

Any TEAE (T-DXd related)

Patients, %

TEAEs in ≥15% of All Patients Treated at the RDE, N=48

Any grade

*There was 1 additional case of drug-related ILD (grade 3) in the HER2-positivecohort at the 3.2-mg/kg dose level

DS-8201: Cumulative ILD data, all phase 3 monotherapy studiesAs of November15, 2020, preliminary data

43

1 Investigator reported grades.

0%

5%

10%

15%


Patie

nts,

%

Patients with ILD by CTCAE Grade from ILD AC2

All cases, regardless of randomization armOngoing controlled phase 3 monotherapy studies (estimated # DS-8201 treated N=979)

Percent presented assumes all cases are observed in the DS-8201 treatment arm

Adjudicated as drug-related ILD

Pending¹

DS-8201: Post-marketing cumulative ILD reported data

44

1,067.2Patient-years

13ILD events reported

2Fatal cases

US (as of November 15, 2020)

16ILD events reported

162.8Patient-years

0Fatal cases

Japan (as of November 15, 2020)

Focusing on the opportunity of DS-8201Increasing our competitive edge

45

Acceleration

Large scale, global program

Aim at 1st line HER2+ mBC, post-neoadjuvant high risk HER2+ early breast cancer and critical role in HER2 low

Broad tumor expansion

Additional work on dose (lung, colorectal), biology (mostly lung) and IHC

IO and DXd technology combine well

02

46


DS-1062 Engineered to be best-in-class TROP2 ADC

47

Humanized anti-TROP2IgG1 mAb

CH 3

F

OHO

O

O

HO

O

N

O

NH O

NH

O

NH

H

O

NH

O

NH

O

O

N HH

N

NCH 3

Cleavable tetrapeptide-based linkerTopoisomerase I inhibitor payload

(DXd)

Deruxtecanb,4

1 Okajima D, et al. Poster presented at: AACR-NCI-EORTC International Conference; October 26-30, 2019; Boston, MA [abstract C026]. 2 Nakada T, et al. Chem Pharm Bull. 2019;67(3):173-185. 3 Daiichi Sankyo Co. Ltd. DS-1062. Daiichi Sankyo.com. Accessed October 6, 2020. https://www.daiichisankyo.com/media_investors/investor_relations/ir_calendar/files/005438/DS-1062%20Seminar%20Slides_EN.pdf 4 Krop I, et al. Oral presentation at: SABCS Symposium; December 10-14, 2019; San Antonio, TX [abstract GS1-03]. 5 Ogitani Y, et al. Cancer Sci. 2016;107(7):1039-1046. a The clinical relevance of these features is under investigation. b Image is for illustrative purposes only; actual drug positions may vary.

• A humanized anti-TROP2 IgG13 monoclonal antibody attached to: • A topoisomerase I inhibitor payload, an exatecan derivative, via• A tetrapeptide-based cleavable linker

Payload mechanism of action: topoisomerase I inhibitor a,1

High potency of payload a,2

Optimized drug to antibody ratio ≈4 a,1

Payload with short systemic half-life a,2

Stable linker-payload a,2

Tumor-selective cleavable linker a,2

Bystander antitumor effect a,2,5

DS-1062 is a DXd ADC composed of 3 components1,2

DS-1062: TROPION-PanTumor01FIH study design and patient disposition

48

Patients with metastatic/unresectable advanced NSCLC• Relapsed from/refractory to standard

treatment (typically includes IO Chemo)

• ECOG PS 0-1• Measurable disease per RECIST v1.1

Unselected for TROP2 expression• Pretreatment tumor tissue required for

retrospective analysis of TROP2 expression

Population

Enrollment complete:• 8.0 mg/kg: 80 patients• 6.0 mg/kg: 50 patients• 4.0 mg/kg: 50 patients• Enrollment completed Oct 2020

Expansion into other tumor types is underway.• TNBC• Other tumor types

Dose expansion

LUNG

TROPION-PanTumor01, Two-part, Multicenter, Open-label, Multiple Dose, First-in-human Study of DS-1062 in Subjects With Advanced Solid Tumors (NCT03401385)

Dose escalation

4.0 mg/kg (n ≈ 3-6)

0.5 mg/kg (n ≈ 3-6)

1.0 mg/kg (n ≈ 3-6)

2.0 mg/kg (n ≈ 3-6)

0.27 mg/kg (n ≈ 3-6)

6.0 mg/kg (n ≈ 3-6)

8.0 mg/kg (n ≈ 3-6)

10.0 mg/kg (n ≈ 3-6)

DS-

1062

Dos

e

49

DS-1062: NSCLCSpider plots of target lesions, based on BICR by dose

Source data on file. Preliminary. DCO: 4 Sept 2020. All patients, regardless of response.

6 mg/kg

8 mg/kg

4 mg/kg

//

DS-1062: NSCLC cumulative ILD, by dose As of September 4, 2020

50

1 Investigator reported grades.

6.8 (14)

1.5 (3)2.9 (6)

1 (2)0

1.5 (3)0 0 0 0 0 0

0%

5%

10%

15%


Patie

nts,

% (#

)

All doses, NSCLC, % (N) (total N=205)

2 (1)

0 0

2 (1)

0 00 0 0 0 0 00%

5%

10%

15%


Patie

nts,

% (#

)

4.0 mg/kg, NSCLC (N=50)

2.2 (1)

0

2.2 (1)

0 0 00 0 0 0 0 00%

5%

10%

15%


Patie

nts,

% (#

)


15 (12)

3.8 (3)

6.3 (5)

1.3 (1)0

3.8 (3)

0 0 0 0 00%

5%

10%

15%


Patie

nts,

% (#

)


Adjudicated as drug-related ILDPending1

DS-1062: TROPION-Lung01Pivotal phase 3 study in post IO/chemo NSCLC

51

LUNG

• NSCLC w/o actionable genomic alterations

• ECOG PS 0 or 1

• Prior treatment with platinum-based chemotherapy and immune check point inhibitor (ICI)

• 1-2 prior therapy regimens

• TROP2 unselected / fresh biopsy obtained for prospective plan to retrospectively test

Key eligibility

Objectives

Primary PFS (BICR)OS

Secondary ORRDoRPROTEAEPK

Exploratory PFS-2BiomarkersExposure/efficacy relationshipsAdditional PRO

N=590Randomize 1:1

StratificationHistology

GeographyLast Tx included ICI

DS-1062 @ 6 mg/kg(N=295)

Docetaxel @ 75 mg/m2

(N=295)

TROPION-Lung01 (not yet listed on Clintrials.gov)

DS-1062NSCLC 1st line / NSCLC activating mutation, breast and beyond

• NSCLC 1st line

IO phase 1 Combinationunder way:– TROPION-Lung02

(+ pembrolizumab) in collaboration with MERCK

– TROPION-Lung04 (+ durvalumab)

• TROPION-Lung05:DS-1062 monotherapy in NSCLC with activating mutations

• TNBC phase 1 cohortNearly complete enrollment, maturing

• Breast cancer substantial plan

• Other tumor cohorts planned

• A bold, large clinical development plan

• Strategy to win with utmost focus in lung and breast cancer

• The very reason we collaborated with AZ

52

Other NSCLC Breast and beyond DS / AZ “game plan”

TROPION-Lung02 (NCT04526691), TROPION-Lung04 (NCT04612751), TROPION-Lung05 (NCT04484142)

02

53


U3-1402: EfficacyPhase 1 study in advanced EGFR-mutated NSCLC

54

++ + +

+ + + + + ++ + + + + + + + + + + + +

+

+ ++-100

-90

-80

-70

-60

-50

-40

-30

-20

-10

0

10

20

30

40

Bes

t cha

nge

in S

oDfr

om b

asel

ine,

%

Confirmed CRConfirmed PRUnconfirmed PRTreatment ongoing (27 of 49 patients [55%])+

N = 49Median follow-up: 5 months

EGFR-mutated NSCLC post TKI and platinum-based chemotherapy Spider plot

-110-100

-90-80-70-60-50-40-30-20-10

010203040

-1 0 1 2 3 4 5 6 7 8 9 10 11 12

40

20

0

–20

–40

–60

–80

–100

Cha

nge

in S

oD fr

om b

asel

ine,

%

CRPRSDPD

N = 49a

Months

Source: Yu et al., ESMO 2020. U31402-U102 (NCT03260491)

LUNG

55

5.6 mg/kg, Q3W

TEAEs n (%) N = 57

TEAEsGrade ≥3Associated with discontinuationAssociated with dose reductionAssociated with dose interruptionAssociated with death

57 (100)38 (67)

5 (9)10 (18)17 (30)

3 (5)

Treatment-emergent SAEsGrade ≥3Treatment related

21 (37)18 (32)11 (19)

Three (5.3%) ILD events were adjudicated by an independent central review committee as U3-1402 related

U3-1402: SafetyPhase 1 study in advanced EGFR-mutated NSCLC

LUNG

Source: Yu et al., ESMO 2020. U31402-U102 (NCT03260491)

0 10 20 30 40 50 60 70

Constipation

Anemia

Alopecia

Vomiting

Neutropenia

Decreased appetite

Thrombocytopenia

Nausea

Fatigue

Patients (%)

Grade ≥3All grades

TEAEs in ≥20% of patients, N=57

Endpoints • Primary endpoint: ORR by BICR• Secondary: DoR, DCR, PFS, OS, safety, immunogenicity, PK

HERTHENA-Lung01: Start in January 2021Pivotal phase 2 study in advanced EGFR-mutated NSCLC

56HERTHENA-Lung01 (NCT04619004)

LUNG

• Metastatic or unresectable NSCLC with EGFR activating mutation (exon 19 deletion or L858R)

• Prior treatment including ≥1 platinum-based chemotherapy regimen and ≥1 EGFR TKI.

• T790M(+) patients must have received osimertinib• Fresh tumor biopsy or recent archived tumor tissue

ARM 1:U3-1402

5.6 mg/kg IV Q3WEnroll up to N = 210

ARM 2:U3-1402

Up-Titration IV Q3WEnroll up to N = 210

Safety, efficacy by BICR, PK, and exposure/responsedata from Phase 1 dose expansion: 5.6 mg/kg fixed dose

and up-titration dose arms (45 patients each)

Decision Point for option to close one arm

R 1:1

U3-1402: Start in January 2021Phase 1 study osimertinib combination in EGFRm NSCLC

57

Metastatic NSCLC with EGFR-activating mutation (exon 19 deletion or L858R)

• Dose Escalation and Dose Expansion Arms 1 and 2: Progression after treatment with osimertinib; no other prior systemic therapies in metastatic setting

• Dose Expansion Cohort 3: No prior systemic treatment for metastatic disease

Pretreatment tumor biopsy or recent archived tumor tissue since progression

Eligibility criteria

Primary• Dose Escalation and Dose Expansion

Cohort 3: Safety and tolerability• Dose Expansion Arms 1 and 2:

ORR by BICR

Secondary• ORR; DCR; DOR• PFS; OS• Safety and tolerability

(dose expansion arms 1 and 2)• Pharmacokinetics• HER3 as a biomarker

(dose expansion only)

ObjectivesDose escalation

Osimertinibdose

Patritumab deruxtecandose

80 mg

1.6 mg/kg

3.2 mg/kg starting dose

4.8 mg/kg

5.6 mg/kg

40 mg

1.6 mg/kg

3.2 mg/kg

4.8 mg/kg

5.6 mg/kg

Guided by BLRM

Dose expansion

U3-1402+ osimertinib at RCD

n ≈ 60

U3-14025.6 mg/kg

n ≈ 60

U3-1402+ osimertinib at RCD

n ≈ 30

Arms 1 and 2 (second-line):

Cohort 3 (first-line):

R 1:1

LUNG

U31402-U103 (not yet listed in Clintrials.gov)

U3-1402: Efficacy in dose expansionPhase 1 study in breast cancer

58

Best Change in Tumor Size by BICR

Source: Krop, et al., Abstract# PD1-09, SABCS Dec 2020; (NCT02980341)

BREAST

U3-1402: Efficacy in dose expansionPhase 1 study in breast cancer

59

Change in Tumor Size by BICR Over Time

BREAST

Source: Krop, et al., Abstract# PD1-09, SABCS Dec 2020

U3-1402: SafetyPhase 1 study in breast cancer

60

n (%)

HER3-high, HR+/HER2-MBC

HER3-low, HR+/HER2-MBC

6.4 mg/kg(n=21)

HER3-high TNBC

6.4 mg/kg(n=31)

U3-1402 Overall(N=116)

4.8 mg/kg(n=33)

6.4 mg/kg(n=31)

Any TEAEGrade ≥3

32 (97.0%)19 (57.6%)

31 (100%)23 (74.2%)

21 (100%)16 (76.2%)

31 (100%)25 (80.6%)

115 (99.1%)83 (71.6%)

TEAE associated with discontinuation3 4 (12.1%) 2 (6.5%) 1 (4.8%) 3 (9.7%) 10 (8.6%)

– No patient discontinued due to thrombocytopenia– 1 drug related AE associated with death (neutropenic sepsis in the HER3-

high 6.4 mg/kg cohort)

• Six (5.2%) ILD events were adjudicated by independent central review committee as related to U3-1402

BREAST

Summary of safetyTreatment-emergent adverse events U3-1402 N=1161


0 10 20 30 40 50 60 70 80 90 100

Nausea

Platelet count decrease

Neutrophil count decrease

Decreased appetite

Vomiting

Diarrhea

Anemia

White blood cell count decrease

Alanine aminotransferase increase

Aspartate aminotransferase increase

Fatigue

Stomatitis

Constipation

Alopecia

Patients (%)

Any gradeGrade ≥3

U3-1402: Instability of HER3 expressionPhase 1 study in breast cancer

61

HER3 expression variability in breast cancer: archival vs pre-treatment biopsy

HER3 expression level decreases during U3-1402 treatment in breast cancer

100%

0%

20%

40%

60%

80%

Archival Biopsy Pre-treatment Biopsy

HER3Membrane PositivityN=56

100%

0%

20%

40%

60%

80%

Pre-treatment Biopsy

On-treatment Biopsy C2D3 or C3D3

HER3Membrane PositivityN=15

BREAST

Source: Krop, et al., Abstract# PD1-09, SABCS Dec 2020. Includes HR+ patients only. C, cycle; D, day.

U3-1402: Pre-treatment HER3 expression vs. response to U3-1402Phase 1 study in breast cancer

62


BREAST

U3-1402: Cumulative ILD data by tumor type As of November 15, 2020

63

1 Investigator reported grades

6.5 (12)

1.6 (3)

2.7 (5)

1.6 (3)

00.5 (1)

0 0 0 0 0 00%

5%

10%

15%


Patie

nts,

% (#

)

Breast Cancer phase 1 (N=184)

Adjudicated as drug-related ILD Pending¹

Patients with CTCAE grade from ILD AC

3.7 (7)

1.6 (3) 1.6 (3)

0.5 (1)0 00 0 0 0 0 0

0%

5%

10%

15%


Patie

nts,

% (#

)

NSCLC phase 1 (N=187)

Adjudicated as drug-related ILD Pending¹

Patients with CTCAE grade from ILD AC

02

64


CE-AlphaEarly DXd-ADC programs

65

Asset Target Potential indications Status

DS-7300 B7-H3(DAR ≈ 4)

Solid tumors(SCCHN, NSCLC, Esophageal, etc.)

FIH: October 2019Delivery model: collaboration with Sarah Cannon, unselected subjectsCurrent status (Phase 1): completed dose level 6 (8 mg/kg); no DLT. Early Clinical Signal with confirmed responses

DS-6157 GPR20(DAR ≈ 8)

GIST FIH: May 2020Delivery model: collaboration with Sarah Cannon; led by Dana Farber Current status (Phase 1): 3rd dose level. No DLT.

DS-6000 CDH6*(DAR ≈ 8)

RCC, Ovarian FIH: FY2020 Q4 (estimated)Delivery model: collaboration with Sarah Cannon

DS-3939 TA-MUC1 Solid tumors FIH: FY2022 (estimated)

Alpha: The cutting edge and power of true innovation delivering drugs changing SOC

*CDH6: cadherin 6

CE-AlphaNon-ADC programs

66

Asset Target Potential indications Status

DS-1055 GARP+Activated T-Reg

Solid tumors FIH October 2020

DS-3201(valemetostat)

EZH1/2 Hematological malignancies ATL: JP phase 2 ongoingGlobal pivotal phase 2 R/R PTCL; FSD FY2021 H1

Axi-CelTM CD-19 CAR-T DLBCL J-NDA approval (December 2020)

Pexidartinib CSF-1R TGCT Phase 3 study: China (FSD December 2020) / Taiwan (FSD September 2020)Phase 3 study: Japan (FSD February 2021)

Quizartinib FLT3 First line AML QuANTUM-First pivotal study; enrollment complete August 2019; results FY2021 H2

Alpha: The cutting edge and power of true innovation delivering drugs changing SOC

03

Our transformation towards being abiologics & multi-modality Company

67

ADC clinical and commercial supply strategyHow we’re delivering on our promises

68

• We are meeting commercial and development obligations with massive scale-up and acceleration

• $1B committed Fall 2019 CAPEX for manufacturing, over FY2020-2022 period

• We’re powering through residual pinch points (DS-1062 supply will not slow down DS / AZ acceleration)

A serial innovator

• Investigate deeply the biology and pharmacology of ADC at the receptor & cellular level:– Gustave Roussy, Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer

Center, Sarah Cannon Research Institute, National Cancer Center (Japan) and other global critical translational science collaborations around our top 3 DXd

• Next ADC constructs: ~FY2022

69

News flow

70

January – March 2021

DS-8201:DESTINY-Lung01 HER2 expressing cohort

DS-1062:Phase 1 NSCLC update

U3-1402:Phase 1 EGFRm NSCLC update

DS-8201:EU DESTINY-Breast01 approvalUS DESTINY-Gastric01 approval

DESTINY-Breast02 dataDESTINY-Breast03 dataDESTINY-Breast04 data

EU DESTINY-Gastric01 submission

Quizartinib:QuANTUM-First data

April – June 2021 Upcoming catalysts

DS-8201:DESTINY-Gastric01, DESTINY-CRC01 updates, biomarker analysis

U3-1402:Phase 1 EGFRm NSCLC update

Contact address regarding this material

Daiichi Sankyo Co., Ltd.Corporate Communications Department

TEL: +81-3-6225-1125Email: [email protected]

mailto:[email protected]

R&D Day 2020

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